在没有纤毛的斑马鱼中，刺猬信号通路受到抑制，但Wnt信号通路正常。
Dampened Hedgehog signaling but normal Wnt signaling in zebrafish without cilia.
作者信息
Huang Peng, Schier Alexander F
机构信息
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard Stem Cell Institute, Broad Institute, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
出版信息
Development. 2009 Sep;136(18):3089-98. doi: 10.1242/dev.041343.
Abstract
Cilia have been implicated in Hedgehog (Hh) and Wnt signaling in mouse but not in Drosophila. To determine whether the role of cilia is conserved in zebrafish, we generated maternal-zygotic (MZ) oval (ovl; ift88) mutants that lack all cilia. MZovl mutants display normal canonical and non-canonical Wnt signaling but show defects in Hh signaling. As in mouse, zebrafish cilia are required to mediate the activities of Hh, Ptc, Smo and PKA. However, in contrast to mouse Ift88 mutants, which show a dramatic reduction in Hh signaling, zebrafish MZovl mutants display dampened, but expanded, Hh pathway activity. This activity is largely due to gli1, the expression of which is fully dependent on Hh signaling in mouse but not in zebrafish. These results reveal a conserved requirement for cilia in transducing the activity of upstream regulators of Hh signaling but distinct phenotypic effects due to differential regulation and differing roles of transcriptional mediators.
摘要
纤毛已被证明在小鼠的刺猬信号通路（Hh）和Wnt信号通路中发挥作用，但在果蝇中并非如此。为了确定纤毛的作用在斑马鱼中是否保守，我们构建了完全缺乏纤毛的母源合子（MZ）卵形（ovl；ift88）突变体。MZovl突变体显示出正常的经典和非经典Wnt信号通路，但在Hh信号通路中存在缺陷。与小鼠一样，斑马鱼的纤毛是介导Hh、Ptc、Smo和PKA活性所必需的。然而，与显示Hh信号通路显著降低的小鼠Ift88突变体不同，斑马鱼MZovl突变体显示出减弱但扩展的Hh信号通路活性。这种活性很大程度上归因于gli1，其表达在小鼠中完全依赖于Hh信号通路，但在斑马鱼中并非如此。这些结果揭示了纤毛在转导Hh信号通路上游调节因子活性方面的保守需求，但由于转录调节因子的差异调节和不同作用而产生了不同的表型效应。
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